1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl compounds and their medical use
View Patent ↗This invention relates to novel 1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl derivatives and their use in the manufacture of pharmaceutical compositions. The compounds of the invention are found to be cholinergic ligands at the nicotinic acetylcholine receptors and modulators of the monoamine receptors and transporters. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.
1. A 1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl compound represented by Formula I
or a pharmaceutically acceptable salt thereof; wherein Ar represents a phenyl, furanyl or thienyl group, which phenyl, furanyl and thienyl is substituted one or more times with bromo.
2. The 1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl compound of claim 1 represented by Formula Ic
or a pharmaceutically acceptable salt thereof; wherein R′ represents bromo; and R″ represents hydrogen.
3. The 1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl compound of claim 1 represented by Formula Id
or a pharmaceutically acceptable salt thereof; wherein R′ represents bromo; and R″ represents hydrogen.
4. The 1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl compound of claim 1 , which is
4-[5-(5-bromo-furan-2-yl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane;
4-[5-(4-bromo-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane;
4-[5-(5-bromo-thiophen-2-yl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane; or
4-[5-(3-bromo-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane;
or a pharmaceutically acceptable salt thereof.
5. A pharmaceutical composition comprising a therapeutically effective amount of the 1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl compound of claim 1 , or a pharmaceutically-acceptable addition salt thereof, together with at least one pharmaceutically-acceptable carrier or diluent.
6. The 1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl compound of claim 1 , which is a compound of Formula Ib
or a pharmaceutically acceptable salt thereof; wherein R′ represents bromo; and R″ represents hydrogen.
7. The 1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl compound of claim 1 , which is 4-[5-(3-bromo-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane; or a pharmaceutically acceptable salt thereof.
8. The 1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl compound of claim 1 , which is 4-[5-(3-bromo-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane fumaric acid salt.